ProjectSummary Unpredictable drug access may play an important role in drug abuse. We know from laboratory studies that behaviormaintainedbynondrugssuchasfoodismorepersistentwithunpredictable(i.e.,variable)schedules of availability than with predictable (i.e., fixed) schedules, and nonhuman subjects choose a variable option over a fixed one even when it costs more in terms of responses per delivery. We recently found that rhesus monkeys choose variable cocaine over a fixed cocaine option, extending work with nondrug reinforcers to a drugofabuse.Inaddition,wehavepreliminarydatashowingthatahistoryofrespondingforcocaineinjections underavariablescheduleincreasescocaineself-administrationunderaprogressive-ratioschedule.Thus,we predictthatunpredictableaccesstodrugsofabuseisanimportantdeterminantofthechoicetotakea drug at the expense of nondrug alternatives and that a history of unpredictable drug access can in- crease the reinforcing effectiveness of drugs. In Specific Aim 1, we will use drug vs. nondrug choice to evaluatethepredictionthatcocainechoicewillbegreatestwhenitisdeliveredunderanunpredictablesched- ule and food under a predictable schedule. Conversely, cocaine choice will be decreased when food is deliv- eredunderanunpredictablescheduleandcocaineunderapredictableschedule.Confirmationofourhypothe- seswouldindicatethatunpredictableavailabilitycontributestoexcessiveallocationofbehaviortowardprocur- ing drugs at the expense of more predictable, nondrug alternatives. If unpredictable food delivery decreases cocaine choice, it would support the use of novel and easily implemented modifications to therapies like con- tingency management or treatments that incorporate nondrug reinforcers. In Specific Aim 2 we hypothesize thatlong-termexposuretoavariablescheduleofcocainedeliverywillincreasetheeffectivenessofcocaineas areinforcerrelativetoaperiodoffixedcocaineexposure,andthiseffectwillbeenhancedwithamoreunpre- dictableVRcomparedtoamorepredictableVR.Confirmationofthispredictionwouldindicatethatunpredicta- bilityisacontributingfactortotheperseverativedrug-seekingbehaviorseenincocaine-dependentindividuals. Thedatacollectedinthisaimwillallowustoevaluatewhetherplacingdrugreinforcersundermorepredictable schedules(asisexperiencedwithagonistreplacementtherapy)canreducesomeofthedeleteriouseffectsof a history of unpredictable access. A reduction in adverse consequences engendered by a switch from unpre- dictabletopredictableschedulesmayrepresentabehavioralmechanismunderlyingagonistreplacementther- apies. Conversely, we will be able to evaluate whether placing a drug with a history of predictable access un- der unpredictable-access conditions exacerbates drug-seeking behavior, which would have implications for effects of discontinuing agonist replacement therapy or prescription drug availability which would represent a transitionfrompredictabledrugaccesstounpredictabledrugaccess(i.e.,returningtoillicitdruguse).